DESCRIPTION (Applicant's abstract): The understanding of how retinal ganglion cells discriminate direction of motion has advanced significantly in recent years, but remains incomplete. A new hypothesis on the mechanisms of retinal directional selectivity postulates that two independent spatially asymmetric pathways converge to the directionally selective ganglion cell. The first facilitates responses to preferred- direction motions and is mediated by an amacrine cell that releases the neurotransmitter acetylcholine. The second inhibits null-direction responses and is mediated by an amacrine cell that releases that neurotransmitter GABA and a bipolar cell that releases glutamate. These two pathways interact locally in individual ganglion-cell dendrites to generate directionally selective responses to motions spanning very short distances. This grant proposal describes three experiments that will scrutinize this hypothesis. The experiments will use On-Off directionally selective ganglion cells of turtles and rabbits. 1) The first experiment will test whether two independent pharmacologically distinct pathways mediate directional selectivity. For this purpose, the investigators will manipulate the retina with pharmacological agents against the neurotransmitters above, while recording the responses of directionally selective ganglion cells. 2) The second experiment will determine whether the synapse between the cholinergic-amacrine and directionally selective ganglion cells has an asymmetric input. To achieve this goal, the investigators will record simultaneously from the amacrine cell that releases acetylcholine and the directionally selective cell. 3) The third experiment will test whether the two putative asymmetric pathways interact locally in dendrites of directionally selective ganglion cells. In this experiment the investigators will image the levels of calcium ions in the dendrites of individual directionally selective ganglion cells. This project should contribute to the understanding of how biophysical mechanisms underlie directional selectivity. Furthermore, the study of retinal directional selectivity will have an impact on the understanding of eye-movement control. Therefore, by elucidating basic brain mechanisms, this project might contribute to finding cures to disorders of the nervous system, and in particular, to those of the visual and oculomotor systems.